Bladder cancer is the second most common genitourinary tumor in human populations, with an incidence of approximately 261,000 new cases each year worldwide; about a third of those are likely to be invasive or metastatic disease at the time of diagnosis (Parkin D M, et al., (1999) CA Cancer J Clin; 49:33-64). Although radical cystectomy is considered the “gold standard” for treatment of patients with localized but muscle-invasive bladder cancer, about 50% of such patients develop metastases within two years after cystectomy and subsequently die of the disease (Sternberg Conn., (1995) Ann Oncol; 6:113-26).
Neoadjuvant chemotherapy is usually prescribed for muscle-invasive bladder cancer to treat micrometastases and to improve resectability of larger neoplasms (Fagg S L, et al., (1984) Br J Urol; 56:296-300, Raghavan D, et al., (1984) Med J Aust; 140:276-8). Regimens involving methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC), followed by radical cystectomy, are more likely to eliminate residual cancer than radical cystectomy alone, and, as such, improve survival among patients with locally advanced bladder cancer ((2003) Lancet; 361:1927-34, Grossman H B, et al., (2003) N Engl J Med; 349:859-66). In some clinical trials, down-staging with drugs prior to surgery was shown to have significant survival benefits (Grossman H B, et al., (2003) N Engl J Med; 349:859-66, Splinter T A, et al., (1992) J Urol; 147:606-8); moreover, patients who respond to neoadjuvant chemotherapy may preserve bladder function and enjoy an improved quality of life. However, since no method yet exists for predicting the response of an individual patient to chemotherapies, such as M-VAC, some patients will suffer from adverse reactions to the drugs without achieving any benefit in terms of positive effects, often losing the opportunity for additional therapy when their physical condition deteriorates. Hence, it is of critical importance to identify molecular targets for the development of novel drugs for bladder cancer patients. Some recent studies have demonstrated that gene expression information generated by cDNA microarray analysis in human tumors can provide molecular phenotyping that identifies distinct tumor classifications not evident by traditional histopathological method (Armstrong, S. A, et al., (2002) Nat Genet, 30: 41-47; Golub, T. R, et al., (1999) Science, 286: 531-537; Hofmann, W. K et al., (2002) Lancet, 359: 481-486). Moreover, several studies have demonstrated the effectiveness of this method for identifying novel cancer-related genes. The promise of such information lies in the potential to improve clinical strategies with neoplastic disease.